Oleogel-mediated Topical Administration of Roflumilast and Paclitaxel as a Synergistic Strategy to Combat Imiquimod-induced Psoriasis.

Psoriasis is a systemic immune disease with severe inflammation and skin thickening. Roflumilast (ROF) blocks cAMP hydrolysis, and paclitaxel (PTX) inhibits cell proliferation; both are effective in topical psoriasis treatment. However, the combination of ROF and PTX has not been reported. This study explored their synergistic mechanism and formulated a ROF-PTX oleogel with strong skin adhesion, low viscosity, enhanced skin penetration, and increased retention. The oleogel, prepared via direct gelation with jojoba oil as oil phase, PPG-15 as solvent, Transcutol as solubilizer, and hydrogenated castor oil as oleogelator. It showed 78.9% holding oil capacity and a viscosity of 0.4049 Pa·s, indicating excellent stability and adhesion. In the imiquimod-induced psoriasis model, the ROF:PTX (1:1) oleogel reduced Baker scores and splenic indices more effectively than ROF or PTX alone. Histological studies suggested that the combination was superior in reducing inflammation and skin thickening. The ROF:PTX (1:1) oleogel group exhibited lower Baker scores and epidermal thickness, demonstrating superior therapeutic efficacy. The H-SCORE revealed a 2.95-fold reduction in IL-17 levels compared to the model group, highlighting the potential of the ROF and PTX combination as an effective psoriasis treatment strategy.